Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway.
Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
Clin Pharmacol Ther. 2018 Mar;103(3):477-484. doi: 10.1002/cpt.770. Epub 2017 Sep 19.
Although pregnancy is known to cause changes in drug pharmacokinetics, little is known about its impact on serum levels of antipsychotics. In this study we retrospectively assessed 201 routine serum antipsychotic therapeutic drug monitoring concentration measurements obtained from a total of 110 pregnancies in 103 women, and 512 measurements from the same women before and after pregnancy. Serum concentrations in the third trimester were significantly lower than baseline for quetiapine (-76%; confidence interval (CI), -83%, -66%; P < 0.001) and aripiprazole (-52%; CI, -62%, -39%; P < 0.001), but not for olanzapine (-9%; CI, -28%, +14%; P = 0.40). For the remaining antipsychotics (perphenazine, haloperidol, ziprasidone, risperidone, and clozapine), our dataset was limited, but it indicates that concentrations may decline at least for perphenazine and possibly also for haloperidol. Even though the clinical consequence of the serum concentrations decline remains to be elucidated, our results warrant close clinical monitoring throughout pregnancy, preferentially supported by therapeutic drug monitoring.
虽然已知妊娠会引起药物药代动力学的变化,但对于其对抗精神病药血清水平的影响知之甚少。在这项研究中,我们回顾性评估了 103 名女性共 110 例妊娠中总共 201 例常规血清抗精神病药治疗药物监测浓度测量值,以及这些女性妊娠前后的 512 例测量值。与基线相比,在妊娠晚期,喹硫平(-76%;置信区间 [CI],-83%,-66%;P < 0.001)和阿立哌唑(-52%;CI,-62%,-39%;P < 0.001)的血清浓度显著降低,但奥氮平(-9%;CI,-28%,+14%;P = 0.40)则不然。对于其余的抗精神病药(奋乃静、氟哌啶醇、齐拉西酮、利培酮和氯氮平),我们的数据有限,但这表明浓度可能至少下降,对于奋乃静,可能也下降。虽然血清浓度下降的临床后果仍有待阐明,但我们的结果证明在整个妊娠期间需要密切的临床监测,最好通过治疗药物监测来支持。